In patients with polyneuritis and paraproteinemia the paraproteins may have antibody activity directed at components of peripheral nerves and clinical improvement may follow treatment directed at lowering the paraprotein concentration. The aim of this project is to identify these patients, define and isolate the peripheral nerve antigens against which the paraproteins are directed, determine whether patients with other types of neuropathies have antibodies to these antigens, and examine the mechanisms regulating the involved B-cell clones. Patients with polyneuritis will be screened for the presence of paraproteins and where found, the paraproteins will be tested for antibody activity against human peripheral nerve components. The paraproteins found to be reactive with peripheral nerve myelin or axons will then be used to identify the specific antigens involved by immunochemical and immunoenzymatic techniques. The antigens will then be purified from solubilized nerve using the paraproteins conjugated to solid phase as affinity reagents. A radioimmune assay to detect antibodies reactive with these antigens will then be developed and used to test for the persence of the antibodies in sera from patients with various idiopathic neuropathies. The isolated antigens and anti-idiotype antibodies raised against the paraproteins will then be used to determine whether the B cells producing the paraproteins are autonomous or subject to regulation by T-cells. The study would improve the detection and classification of patients with peripheral neuropathies, allow the identification of patients who would benefit from therapeuric intervention, identify antigens which might be important in other autoimmune diseases of the central or peripheral nervous system, and yield insights into the mechanisms regulating the disease state so that more effective therapeutic measures can be developed.